11 November 2012

Using Fluvastatin As Treatment For Antiphospholipid Syndrome (APS)

Research show that fluvastatin, a cholesterol lowering statin, can be used as treatment for antiphospholipid syndrome (APS). APS is a disorder that can cause pregnancy loss, stroke, myocardial infarction, and arterial/deep vein thrombosis.

Antiphospholipid syndrome is an autoimmune disorder that causes or provokes blood clots and miscarriages. APS increases the risk of deep vein thrombosis (blood clot in the veins) and arterial thrombosis (blood clot in an artery). A thrombus or a blood clot in a blood vessel can lead to a heart attack or stroke.
APS is also known as "Hughes Syndrome". It is named after Dr. Graham R.V. Hughes who has done extensive research on this disorder.

People of all ages, from children to adults, can have APS. Although women aged 18 to 40 are more likely to be affected (five times more women have APS than men).

APS is caused when the body's own immune system start producing antiphospholipid antibodies (aPLs). These antibodies work against a cell membrane substance called the phospholipid. Once the antiphospholipid binds to the phospholipid, the blood is more likely to clot.

For some individuals, the production of aPLs is not harmful nor does it cause any health complications. But for others, these antibodies can cause cause inflammation and increase the risk for the formation of clots.

It is not known what causes the immune system to start producing this antibody but it is believed that both genetic and environmental factors may be involved.

Video: What is Hughes Syndrome (Antiphospholipid Antibody Syndrome)?

There is no cure for antiphospholipid syndrome but there are treatments that can reduce the risk of a blood clot once APS is diagnosed correctly. Usually drug treatments involve anticoagulants and antiplatelets which prevents blood from clotting.

Warfarin and Heparin are commonly used anticoagulants while aspirin is the most popular antiplatelet. The difference between the two is that anticoagulants basically thins the blood so clots are harder to form while antiplatelets decrease platelet aggregation and inhibit thrombus formation.

Statins As Treatment for APS

New research suggests that statins, traditionally used for cholesterol lowering, could be used in the management of individuals who are at risk for developing clotting because they have autoimmune antiphospholipid antibodies (aPL). The research will be presented in two presentations at the annual meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP).

"What we have shown is that inflammatory and thrombotic proteins are elevated in aPL-positive patients and that statins can decrease these proteins," said Doruk Erkan, MD, an associate attending rheumatologist and clinician researcher at Hospital for Special Surgery in New York City, who was one of the two main investigators in the study together with Silvia Pierangeli, Ph.D., at University of Texas Medical Branch, Galveston, Texas. The researchers note that statins would not be useful in treating individuals who are at risk for pregnancy loss because of aPLs—statins are contraindicated (medication or treatment should not be used) during pregnancy.

For years, researchers have known that aPLs can trigger the production of proteins that can cause inflammation and increase the risk of formation of clots. While some aPL-positive individuals develop blood clots, strokes, and pregnancy complications, others are perfectly healthy. Individuals who are aPL-positive and have either venous thrombosis, arterial thrombosis, or fetal loss are classified as having antiphospholipid syndrome (APS).

The new research was a collaborative effort between investigators at Hospital for Special Surgery and the University of Texas Medical Branch, Galveston, Texas. Investigators enrolled 41 patients who were aPL-positive, some of whom were healthy and some who had APS. They tested their blood for 12 inflammatory and thrombotic (clot forming) proteins, and then compared the results to data from 30 healthy patients who were aPL negative. These controls were matched for sex and age. Nine of the 12 proteins were elevated in aPL-positive patients compared to healthy controls.

The researchers then set out to test whether a statin called fluvastatin could reduce the proteins that were elevated in the individuals with aPLs. "Statins do more than just lowering cholesterol. They also have anti-inflammatory effects," said Dr. Pierangeli. The 41 aPL-positive patients were given 40 mg of fluvastatin daily for three months and then were instructed to stop taking the drug. Investigators collected blood samples and measured the levels of the inflammatory and thrombotic proteins at baseline and monthly thereafter for six months.

Of the 24 patients who completed the study, the researchers found that fluvastatin significantly decreased the levels of eight of the 12 proteins, all of which had been elevated in aPL-positive individuals compared with controls. The investigators also found that when patients stopped taking the fluvastatin, the levels of six proteins rebounded to high levels.

"Following Dr. Pierangeli's mouse experiments in which statins decreased inflammatory proteins induced by aPL, this is the first prospective study analyzing these proteins in aPL-positive patients before and after treatment with fluvastatin," said Dr. Erkan. "Launching a randomized trial to determine the effect of statins on clinical outcomes is the logical next step."